Gene Expression and Antiviral Activity of Interleukin-35 in Response to Influenza A Virus Infection

Wang, Li; Zhu, Shengli; Xu, Gang; Feng, Jian; Han, Tao; Zhao, Fanpeng; She, Yuanbin; Shi, Lei; Ye, Linbai; Zhu, Ying

doi:10.1074/jbc.m115.693101

Cited by 14 publications

(11 citation statements)

References 69 publications

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“…Similarly, IAV also enhances IL-35 in peripheral blood mononuclear cells, throat swabs [71], human primary lung cells, and PBMCs that induce IFN-γ expression [70]. Unlike HBV infection, NF-κb is the key component that mediates IL-35 transcription during IAV infection, and IL-35 may suppress IAV protein synthesis by inducing type I and type III IFN [71]. Furthermore, STAT1 and STAT4 signaling pathways must be activated for effective function of IL-35.…”

Section: Anti-viral Functionsmentioning

confidence: 99%

Immunoregulatory Functions of the IL-12 Family of Cytokines in Antiviral Systems

Guo

Cao

Zhu

2019

Viruses

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Members of the interleukin 12 (IL-12) family have been known to be inflammatory factors since their discovery. The IL-12 family consists of IL-12, IL-23, IL-27, IL-35, and a new member, IL-39, which has recently been identified and has not yet been studied extensively. Current literature has described the mechanisms of immunity of these cytokines and potential uses for therapy and medical cures. IL-12 was found first and is effective in combatting a wide range of naturally occurring viral infections through the upregulation of various cytokines to clear the infected cells. IL-23 has an essential function in immune networks, can induce IL-17 production, and can antagonize inhibition from IL-12 in the presence of T helper (Th) 17 cells, resulting in type II IFN (IFN-γ) regulation. IL-27 has a competitive relationship to IL-35 because they both include the same subunit, the Epstein–Barr virus-induced gene3 (EBi3). This review provides a simple introduction to the IL-12 family and focuses on their functions relevant to their actions to counteract viral infections.

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Section: Anti-viral Functionsmentioning

confidence: 99%

Immunoregulatory Functions of the IL-12 Family of Cytokines in Antiviral Systems

Guo

Cao

Zhu

2019

Viruses

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“…IL-35 was increasingly expression in gingival tissue and gingival crevicular fluid in chronic bacterial infection induced periodontitis (Mitani et al, 2015 ). Influenza A virus infection also induced enhancement of IL-35 in both peripheral blood mononuclear cells (PBMCs) and human primary lung cells (Chen et al, 2016 ; Wang et al, 2016 ). The elevation of IL-35 exhibited extensive antiviral activity against various viral infections (Wang et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-35 Suppresses Antiviral Immune Response in Chronic Hepatitis B Virus Infection

Shao

Jia

et al. 2017

Front. Cell. Infect. Microbiol.

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The mechanisms of hepatitis B virus (HBV) persistent infection are not completely understood. Interleukin (IL)-35, which is a newly identified cytokine belongs to IL-12 family, has been demonstrated to induce immunotolerance. Thus, the aim of current study was to investigate the role of IL-35 during chronic HBV infection. A total of 61 patients with chronic HBV infection [37 chronic hepatitis B (CHB) and 24 asymptomatic HBV carriers (ASC)] and 20 healthy individuals were enrolled. IL-35 concentration as well as the modulatory function of IL-35 on CD4+CD25+CD127dim/− regulatory T cells (Tregs) and on HBV antigen-specific CD8+ T cells was investigated. IL-35 expression was significantly increased in both CHB and ASC, and was positively correlated with the levels of HBV DNA. Inhibition of viral replication induced the reduction in serum levels of IL-35. IL-35 stimulation led to inhibition of proinflammatory cytokine productions and elevation of apoptosis in peripheral blood mononuclear cells (PBMCs), but not in HepG2.2.15 cells. Moreover, IL-35 stimulation not only robustly inhibited cellular proliferation, but also up-regulated the production of IL-10 and IL-35 in a HBV antigen-specific and non-specific manner in Tregs/CD4+CD25− T cells coculture system, which indicated enhancement of suppressive function of Tregs. Furthermore, IL-35 also reduced both cytolytic activity (direct lysis of HepG2.2.15 cells) and noncytolytic function (IFN-γ and TNF-α production) of HBV antigen-specific CD8+ T cells. The current data suggested that IL-35 contributed to maintain viral persistence by suppressing antiviral immune responses and reducing inflammatory responses in chronic HBV infection.

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“…Curiously, our findings for IL-35 differ from a study, in which serum levels of IL-35 were significantly increased in the cirrhotic process (43) and regulated the functions of viral-specific Tregs and CD8 + T cells during chronic HBV infection, which might contribute to immunotolerance and viral persistence (33,42). However, a recent study showed that IL-35 play contradictory roles in controlling viral persistence and inhibiting inflammatory responses and have an immunosuppressive function in chronic hepatitis C virus (HCV) infection (33) and another study suggests that influenza A virus infection can induce IL-35 expression and IL-35 can activate the IFN pathway and may have a potential antiviral activity (54). These findings suggest that further studies are necessary for a better understanding of the complex regulatory mechanisms of the host antiviral response related to IL-35 during HBV infection.…”

Section: Discussionmentioning

confidence: 99%

Cytokine, Genotype, and Viral Load Profile in the Acute and Chronic Hepatitis B

et al. 2020

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Several hepatitis B virus (HBV) factors, including viral load, genotype, genome mutations, and cytokine production, have been reported to be associated with different risks of progression of liver disease. The aim of this study was to verify if there is an association among the levels of cytokines (interleukin [IL]-35, IL-6, IL-17A, interferon [IFN]-c) in the plasma, viral load, and the different genotypes of HBV in patients with acute or chronic hepatitis B. Methods: 49 serum samples, 20 from acute and 29 from chronic cases, were submitted to a real-time and nested-polymerase chain reaction to quantify, detect, and genotype HBV DNA. The cytokines IL-35, IL-6, IL-17A, and IFN-c were detected by an enzyme-linked immunosorbent assay (ELISA). The median viral load was 3.15 log 10 IU DNA/mL and 2.90 log 10 IU DNA/mL for acute and chronic patients, respectively. Genotype A, D, E, and F were identified in chronic carriers of HBV infection, while only genotype A and F were identified in individuals with acute infection. IFN-c (p = 0.024) and IL-17A (p = 0.046) levels were significantly increased in chronic patients and IL-6 and IL-35 were higher in patients with acute infection, however, without statistical difference. IL-17A and IFN-c can be modulating proinflammatory effects and inducing hepatocellular damage, in chronic patients, and IL-6 and IL-35 may be involved in viral elimination and protection against chronicity during the acute phase of infection. These results can contribute to understanding of the complex regulatory mechanisms of the host antiviral response related to cytokine production during acute and chronic HBV infection.

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Gene Expression and Antiviral Activity of Interleukin-35 in Response to Influenza A Virus Infection

Abstract: Interleukin-35 (IL-35

Cited by 14 publications

References 69 publications

Immunoregulatory Functions of the IL-12 Family of Cytokines in Antiviral Systems

Immunoregulatory Functions of the IL-12 Family of Cytokines in Antiviral Systems

Interleukin-35 Suppresses Antiviral Immune Response in Chronic Hepatitis B Virus Infection

Cytokine, Genotype, and Viral Load Profile in the Acute and Chronic Hepatitis B

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